Chassot Anne-Amandine, Ranc Fariba, Gregoire Elodie P, Roepers-Gajadien Hermien L, Taketo Makoto M, Camerino Giovanna, de Rooij Dirk G, Schedl Andreas, Chaboissier Marie-Christine
INSERM, U636, F-06108 Nice, France.
Hum Mol Genet. 2008 May 1;17(9):1264-77. doi: 10.1093/hmg/ddn016. Epub 2008 Feb 4.
The sex of an individual is determined by the fate of the gonad. While the expression of Sry and Sox9 is sufficient to induce male development, we here show that female differentiation requires activation of the canonical beta-catenin signaling pathway. beta-catenin activation is controlled by Rspo1 in XX gonads and Rspo1 knockout mice show masculinized gonads. Molecular analyses demonstrate an absence of female-specific activation of Wnt4 and as a consequence XY-like vascularization and steroidogenesis. Moreover, germ cells of XX knockout embryos show changes in cellular adhesions and a failure to enter XX specific meiosis. Sex cords develop around birth, when Sox9 becomes strongly activated. Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development.
个体的性别由性腺的命运决定。虽然Sry和Sox9的表达足以诱导雄性发育，但我们在此表明，雌性分化需要经典β-连环蛋白信号通路的激活。β-连环蛋白的激活在XX性腺中由Rspo1控制，Rspo1基因敲除小鼠表现出性腺雄性化。分子分析表明，Wnt4缺乏雌性特异性激活，结果导致XY样血管生成和类固醇生成。此外，XX基因敲除胚胎的生殖细胞显示细胞黏附发生变化，并且无法进入XX特异性减数分裂。性索在出生前后发育，此时Sox9被强烈激活。因此，Sox9激活与β-连环蛋白激活之间的平衡决定了性腺的命运，Rspo1作为雌性发育所需的经典β-连环蛋白信号的关键调节因子发挥作用。
